Article: Celecoxib

Celecoxib
Systematic (IUPAC) name
4-[5-(4-methylphenyl)-3-(trifluoromethyl) pyrazol-1-yl]benzenesulfonamide
Identifiers
CAS number	169590-42-5
ATC code	L01XX33 M01AH01
PubChem	2662
DrugBank	APRD00373
Chemical data
Formula	C17H14N3F3O2S
Mol. weight	381.373 g/mol
Pharmacokinetic data
Bioavailability	?
Protein binding	97% (mainly to albumin)
Metabolism	Hepatic (mainly CYP2C9)
Half life	~11 hours
Excretion	Renal 27%, faecal 57%
Therapeutic considerations
Pregnancy cat.	B3 (Au)
Legal status	℞ Prescription only
Routes	Oral

Celecoxib (INN) (IPA: [sɛlɛˈkɒksɪb]) is a non-steroidal anti-inflammatory drug (NSAID) used in the treatment of osteoarthritis, rheumatoid arthritis, acute pain, painful menstruation and menstrual symptoms, and to reduce numbers of colon and rectum polyps in patients with familial adenomatous polyposis. It is marketed by Pfizer under the brand name Celebrex.

Pharmacology

Celecoxib is a highly selective COX-2 inhibitor and primarily inhibits this isoform of cyclooxygenase, whereas traditional NSAIDs inhibit both COX-1 and COX-2. Celecoxib is approximately 10-20 times more selective for COX-2 inhibition over COX-1. In theory, this specificity allows celecoxib and other COX-2 inhibitors to reduce inflammation (and pain) while minimizing gastrointestinal adverse drug reactions (e.g. stomach ulcers) that are common with non-selective NSAIDs. It also means that it has a reduced effect on platelet aggregation compared to traditional NSAIDs.

Adverse effects

Main article: Non-steroidal anti-inflammatory drug

Aside from the incidence of gastric ulceration, celecoxib exhibits a similar adverse drug reaction (ADR) profile to other NSAIDs.

Gastrointestinal ADRs

In theory the COX-2 selectivity should result in a significantly lower incidence of gastrointestinal ulceration than traditional NSAIDs. The main body of evidence touted to support this theory were the preliminary (6 month) results of the Celecoxib Long-term Arthritis Safety Study (CLASS) as published in 2000, which demonstrated a significant reduction in the incidence of gastrointestinal ulceration in those taking celecoxib versus ibuprofen or diclofenac. (Silverstein et al, 2000) The final (12 month) results from the CLASS study, however, did not indicate any advantage of celecoxib over the other NSAIDs in the study. (Malhotra, Shafiq & Pandhi, 2004)

Cardiovascular risk

The withdrawal of rofecoxib from the market in 2004 due to an increased risk of adverse cardiovascular events led to the suspicion that this was a class effect. Indeed an increased risk of heart attack and stroke was found in a National Cancer Institute study studying the use of 400-800 mg celecoxib daily for the prevention of colorectal adenoma (relative risk 2.3-3.4 vs placebo). (Solomon et al., 2005)

There is still much conjecture, however, as to whether this risk is significant for the majority of patients being treated with lower doses for osteoarthritis. The overall safety profile of celecoxib, including its cardiovascular, renal and digestive effects, will be compared to traditional anti-inflammatories (naproxen and ibuprofen) in a randomized trial of 20,000 high risk patients that is due to begin in 2006 (PRECISION study sponsored by Pfizer)

Allergy

Celecoxib contains a sulfonamide moiety and may cause allergic reactions in those allergic to other sulfonamide-containing drugs. This is in addition to the contraindication in patients with severe allergies to other NSAIDs.

Commercial history

Celecoxib was developed by G. D. Searle & Company and marketed jointly by Searle and Pfizer under the brand name Celebrex. Searle was acquired by Pharmacia, which was then acquired by Pfizer, in part so that Pfizer could take full control of Celebrex.

Celecoxib is available by prescription in capsule form.